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Aquaglyceroporin 1 (AQP1) is a membrane channel that, in\n                    <jats:italic>L. major<\/jats:italic>\n                    , localizes to the flagellum and mediates antimony uptake and cell-volume regulation. Here, we show that in\n                    <jats:italic>L. amazonensis<\/jats:italic>\n                    AQP1 is instead targeted to glycosomes and that its expression is modulated by iron availability. A CRISPR-Cas9\u2013mediated knockout of AQP1 in\n                    <jats:italic>L. amazonensis<\/jats:italic>\n                    revealed its multifunctional importance. AQP1-null promastigotes displayed a significant growth defect, particularly under iron-depleted conditions, and were impaired in regulating cell volume under osmotic stress. The mutant parasites contained approximately 50% less intracellular iron than wild-type cells and showed an increase in total superoxide dismutase activity, underscoring a role for AQP1 in iron homeostasis and oxidative stress management. AQP1 deletion also markedly reduced virulence in murine macrophages and in infected mice. Strikingly, loss of AQP1 increased resistance to trivalent antimony (Sb\n                    <jats:sup>III<\/jats:sup>\n                    ), a first-line antileishmanial drug. AQP1-knockout promastigotes showed a 70% increase in Sb\n                    <jats:sup>III<\/jats:sup>\n                    IC\n                    <jats:sub>50<\/jats:sub>\n                    and accumulated more Sb intracellularly than wild-type, suggesting an altered antimony handling. Altogether,\n                    <jats:italic>L. amazonensis<\/jats:italic>\n                    AQP1 is a glycosomal protein that links iron metabolism, osmoregulation, and antimony susceptibility. Its glycosomal targeting and multifaceted roles differ from those of AQP1 orthologs in other\n                    <jats:italic>Leishmania<\/jats:italic>\n                    species. These findings suggest the existence of additional antimony uptake mechanisms beyond AQP1, with implications for understanding drug resistance.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0014141","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:28:32Z","timestamp":1775150912000},"page":"e0014141","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Glycosomal Aquaglyceroporin 1 dual role in iron homeostasis and antimony susceptibility in Leishmania amazonensis"],"prefix":"10.1371","volume":"20","author":[{"given":"Romario Lopes","family":"Boy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Andrade","family":"Zampieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana 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